Oculopharyngeal muscular dystrophy (OPMD) is caused by polyalanine expansion in nuclear protein PABPN1 [poly(A) binding protein nuclear 1] and characterized by muscle degeneration. Druggable modifiers of proteotoxicity in degenerative diseases, notably the longevity modulators sirtuins, may constitute useful therapeutic targets. However, the modifiers of mutant PABPN1 are unknown. Here, we repo...

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disease characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness. The autosomal dominant form of the disease is caused by short (GCG)(8-13) expansions in the PABP2 gene. This gene encodes the poly(A) binding protein 2 (PABP2), an abundant nuclear protein that binds with high affinity to nascent p...

The effect of confinement on the stability and dynamics of peptides and proteins is relevant in the context of a number of problems in biology and biotechnology. We have examined the stability of different helix-forming sequences upon confinement to a carbon nanotube using Langevin dynamics simulations of a coarse-grained representation of the polypeptide chain. We show that the interplay of se...

Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset disorder characterized by progressive eyelid drooping, swallowing difficulties and proximal limb weakness. The autosomal dominant form of this disease is caused by short expansions of a (GCG)(6) repeat to (GCG)(8-13) in the PABPN1 gene, which results in the expansion of a polyalanine stretch from 10 to 12-17 alanines in the N-terminus ...

Peptide self-assembly plays a role in a number of diseases, in pharmaceutical degradation, and in emerging biomaterials. Here, we aim to develop an accurate molecular-scale picture of this process using a multiscale computational approach. Recently, Shell (Shell, M. S. J. Chem. Phys. 2008, 129, 144108-7) developed a coarse-graining methodology that is based on a thermodynamic quantity called th...

Various spider species produce dragline silks with different mechanical properties. The primary structure of silk proteins is thought to contribute to the elasticity and strength of the fibres. Previously published work has demonstrated that the dragline silk of Euprosthenops sp. is stiffer then comparable silk of Nephila edulis, Araneus diadematus and Latrodectus mactans. Our studies of Eupros...

BACKGROUND Tetralogy of Fallot (ToF), the most frequent cyanotic congenital heart disease, is associated with a wide range of intra- and extracardiac phenotypes. In order to get further insight into genotype-phenotype correlation, a large cohort of 230 unselected patients with ToF was comprehensively investigated. METHODS AND RESULTS 230 patients with ToF were studied by karyotyping, comprehe...